Organocatalytic Michael addition–lactonisation of carboxylic acids using α,β-unsaturated trichloromethyl ketones as α,β-unsaturated ester equivalents

The authors thank the Royal Society for a University Research Fellowship (ADS), The Carnegie Trust for the Universities of Scotland (LCM), Syngenta/EPSRC (Case award to DGS), GSK/EPSRC (CASE award to SRS), the EU (IEF for CS), and the European Research Council under the European Union's Seventh Framework Programme (FP7/2007-2013) ERC Grant Agreement no. 279850 (JET) for funding.Isothiourea HBTM-2.1 catalyses the Michael addition-lactonisation of 2-aryl and 2-alkenylacetic acids and α,β-unsaturated trichloromethyl ketones. Ring-opening of the resulting dihydropyranones and subsequent alcoholysis of the CCl ketone with an excess of methanol gives a range of diesters in high diastereo- and enantioselectivity (up to 95:5 dr and >99% ee). Sequential addition of two different nucleophiles to a dihydropyranone gives the corresponding differentially substituted diacid derivative.PostprintPeer reviewe